Complementary therapeutic strategies are required to destroy solid tumors and inhibit regrowth of metastatic or residual primary tumor. In theory, the combination of radiation therapy and antiangiogenesis therapy fully meet these requirements. We have preliminary data using a potent antiangiogenic designed peptide, Anginex, indicating preferential tumor binding, tumor growth inhibition and synergistic anti-tumor effects in combination with radiotherapy equal or better than angiostatin or Sugen 6668 and radiation against our tumor models. Anginex is a non-toxic and stable beta-sheet forming 33-mer, developed at the University of Minnesota. We, and others, have recently demonstrated the potential of various anti-vascular or anti-angiogenic compounds to impact the success of radiation therapy via a modification of the existing tumor physiology or tumor endothelial radiosensitivity. Therefore, the use of Anginex to enhance radiation response represents a rational and prudent approach to develop better methods of cancer therapy. This project aims to maximize our understanding of the effects of Anginex on tumor physiology and radiation response and the influence of circulating endothelial cells on these processes. The three specific aims of this work will (1) expand our initial observations that tumor growth is retarded and radiation response in enhanced with the application of Anginex (2) assess the mechanism of Anginex binding and radiosensitization of tumor-endothelium and anginex effect on endothelial progenitor cells (3) Elucidate the effects of anginex treatment and fractionated radiotherapy on one another and on the role of circulating endothelial cells during fractionated treatment. The information to be obtained in this study will be a vital part of design and implementation of large animal and human clinical trials.